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INVESTIGATING IMMUNE ESCAPE MECHANISMS BETWEEN
HIGH & LOW RISK MUCOSAL HUMAN PAPILLOMAVIRUS GENOTYPES AND CUTANEOUS HUMAN PAPILLOMAVIRUS GENOTYPES
by
Carly Anne Movius
___________________________________________________________
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(MOLECULAR MICROBIOLOGY AND IMMUNOLOGY)
May 2011
Copyright 2011 Carly Anne Movius

Cervical cancer is associated with high risk HPV genotypes 93 % of the time. HPV infections can take months and even up to a year to clear, and 30 % of HPV infections will develop into cervical cancer. A novel immune suppression mechanism used by HPV16 has been characterized in Langerhans Cells (LCs), such that there is an activation of PI3K pathway and a down regulation of AKT pathways, mediated in part by PP2A. HPV16 suppresses phenotypic activation and immune function in LCs. This study reveals that other high risk mucosal HPV genotypes (HPV18, HPV31 and HPV45) and a low risk mucosal HPV genotype (HPV11) and a cutaneous HPV genotype (HPV5) share this particular immune escape mechanism based on a conserved sequence in L2 minor capsid protein (aa 108-126). However, a cutaneous HPV genotype (HPV1) does not share this immune escape mechanism in LCs, as there is little homology to the HPV16 L2 sequence (aa 108-126). In addition this study shows that this particular immune suppression mechanism can be reversed with intracellular toll-like receptor (TLR) agonists 3 and 8, but only marginally with a TLR3 agonist. This demonstrates the possibility for therapeutic compounds such as these which could be developed to treat the 10 % of the world’s population currently estimated to be infected with HPV, as an alternative treatment to ablative surgical procedures.

INVESTIGATING IMMUNE ESCAPE MECHANISMS BETWEEN
HIGH & LOW RISK MUCOSAL HUMAN PAPILLOMAVIRUS GENOTYPES AND CUTANEOUS HUMAN PAPILLOMAVIRUS GENOTYPES
by
Carly Anne Movius
___________________________________________________________
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(MOLECULAR MICROBIOLOGY AND IMMUNOLOGY)
May 2011
Copyright 2011 Carly Anne Movius